Optimizing the aldosterone-to-renin ratio cut-off for screening primary aldosteronism based on cardiovascular risk: a collaborative study.

OBJECTIVES: Aldosterone-to-renin ratio (ARR) based screening is the first step in the diagnosis of primary aldosteronism (PA). However, the guideline-recommended ARR cutoff covers a wide range, from the equivalent of 1.3 to 4.9 ng·dl-1/mIU∙l-1. We aimed to optimize the ARR cutoff for PA screening based on the risk of cardiovascular diseases (CVD). METHODS: Longitudinally, we included hypertensive participants from the Framingham Offspring Study (FOS) who attended the sixth examination cycle and followed up until 2014. At baseline (1995-1998), we used circulating concentrations of aldosterone and renin to calculate ARR (unit: ng·dl-1/mIU∙l-1) among 1,433 subjects who were free of CVD. We used spline regression to calculate the ARR threshold based on the incident CVD. We used cross-sectional data from the Chongqing Primary Aldosteronism Study (CONPASS) to explore whether the ARR cutoff selected from FOS is applicable to PA screening. RESULTS: In FOS, CVD risk increased with an increasing ARR until a peak of ARR 1.0, followed by a plateau in CVD risk (hazard ratio 1.49, 95%CI 1.19-1.86). In CONPASS, when compared to essential hypertension with ARR < 1.0, PA with ARR ≥ 1.0 carried a higher CVD risk (odds ratio 2.24, 95%CI 1.41-3.55), while essential hypertension with ARR ≥ 1.0 had an unchanged CVD risk (1.02, 0.62-1.68). Setting ARR cutoff at 2.4 ~ 4.9, 10% ~30% of PA subjects would be unrecognized although they carried a 2.45 ~ 2.58-fold higher CVD risk than essential hypertension. CONCLUSIONS: The CVD risk-based optimal ARR cutoff is 1.0 ng·dl-1/mIU∙l-1 for PA screening. The current guideline-recommended ARR cutoff may miss patients with PA and high CVD risk. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03224312).

Neuroimaging mechanisms in short-term heroin- and methamphetamine-abstinent users: Similarities and differences.

Heroin and methamphetamine cause great damage to individuals and society. However, numerous withdrawal mechanisms remain unidentified. In this study, 19 heroin short-term abstinent (HSTA) patients, 20 methamphetamine short-term abstinent (MSTA) patients, and 27 healthy controls (HCs) were scanned using multimodal magnetic resonance imaging. Degraded nodes of fiber tracts were identified using automated fiber quantification. Voxel- and surface-based morphometric measurements were performed to determine the gray matter volume and cortical thickness. The MSTA and HSTA groups had abnormal diffusion metrics in a variety of bilateral corticospinal tract (CST) and left superior longitudinal tract (SLT) nodes compared with the HC group. The MSTA patients reported more severely disrupted diffusion metrics in certain nodes of the bilateral anterior thalamic radiation and left inferior fronto-occipital tract than the HSTA patients. The MSTA and HSTA groups exhibited identical cortical damage in the fusiform and superior temporal gyri, as well as in the superior frontal gyrus, posterior cerebellum, and precentral gyrus. Extensive differences in gray matter lesions were observed between the MSTA and HSTA groups. Neuroimaging mechanisms of short-term abstinence may aid in the development of rehabilitation strategies.

Impairments in the Default Mode and Executive Networks in Methamphetamine Users During Short-Term Abstinence.

Purpose: Methamphetamine use may cause severe neurotoxicity and cognitive impairment, leading to addiction, overdose, and high rates of relapse. However, few studies have systematically focused on functional impairments detected by neuroimaging in methamphetamine abstainers (MAs) during short-term abstinence. This study aimed to investigate effective connectivity, resting-state networks, and internetwork functional connectivity in MA brains to improve clinical treatment. Methods: Twenty MAs and 27 age- and education-matched healthy controls underwent resting-state functional magnetic resonance imaging. The amplitude of low-frequency fluctuations and Granger causality were analyzed to investigate disrupted brain regions and effective connectivity, respectively. Independent component analysis and functional network connectivity were used to identify resting-state networks and internetwork functional connectivity, respectively. Results: Compared with healthy controls, MAs demonstrated abnormal amplitudes of low-frequency fluctuations in the bilateral precuneus, left posterior cingulate cortex (PCC), left middle frontal gyrus (MFG), left superior parietal lobule, left supplementary motor area (SMA), and left inferior parietal lobule (IPL). Moreover, MAs showed decreased effective connectivity from the left PCC to the left precuneus, increased effective connectivity from the left precuneus to the left MFG and from the right precuneus to the left SMA, and altered functional connectivity within the default mode network (DMN), frontoparietal network, sensorimotor network, ventral attention network, cerebellar network, and visual network. Importantly, hyperconnectivity between the DMN and ventral attention network and hypoconnectivity between the DMN and cerebellar network as well as the DMN and frontoparietal network were demonstrated in MAs. Conclusion: Our study implies that in short-term methamphetamine abstinence, disruptions to the DMN and executive network may a play key role, providing new insights for early rehabilitation.

Evaluation of White Matter Microstructural Alterations in Patients with Post-Stroke Cognitive Impairment at the Sub-Acute Stage.

Purpose: To investigate white matter alterations in post-stroke cognitive impairment (PSCI) patients at the subacute stage employing diffusion kurtosis and tensor imaging. Methods: Thirty PSCI patients at the subacute phase and 30 healthy controls (HC) underwent diffusion kurtosis imaging (DKI) scans and neuropsychological assessments. Based on the tract-based spatial statistics and atlas-based ROI analysis, fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), kurtosis fractional anisotropy (KFA), axial kurtosis (AK), and radial kurtosis (RK) were compared in specific white matter fiber bundles between the groups (with family-wise error correction). Adjusting for age and gender, a partial correlation was conducted between neurocognitive assessments and DKI metrics in the PSCI group. Results: In comparison with the HC, PSCI patients significantly showed decreased MK, RK, and FA and increased MD values in the genu of corpus callosum, anterior limb internal capsule, and left superior corona radiata. In addition, DKI detected more white matter region changes in MK (31/48), KFA (40/48), and RK (25/48) than DTI with FA (28/48) and MD (21/48), which primarily consisted of the right cingulum, right superior longitudinal fasciculus, and left posterior limb of internal capsule. In the left anterior limb of internal capsule, MK and RK values were significantly negatively correlated with TMT-B (r = -0.435 and -0.414, P < 0.05), and KFA values (r = -0.385, P < 0.05) of corpus callosum negatively associated with TMT-B. Conclusion: Combing DTI, DKI, and neuropsychological tests, we found extensive damaged white matter microstructure and poor execution performance in subacute PSCI patients. DKI could detect more subtle white matter changes than DTI metrics. Our findings provide added information for exploring the mechanisms of PSCI and conducting cognitive rehabilitation in the subacute stage.

Olfactory Deprivation Hastens Alzheimer-Like Pathologies in a Human Tau-Overexpressed Mouse Model via Activation of cdk5.

Olfactory dysfunction is a recognized risk factor for the pathogenesis of Alzheimer's disease (AD), while the mechanisms are still not clear. Here, we applied bilateral olfactory bulbectomy (OBX), an olfactory deprivation surgery to cause permanent anosmia, in human tau-overexpressed mice (htau mice) to investigate changes of AD-like pathologies including aggregation of abnormally phosphorylated tau and cholinergic neuron loss. We found that tau phosphorylation in hippocampus was increased at Thr-205, Ser-214, Thr-231, and Ser-396 after OBX. OBX also increased the level of sarkosyl-insoluble Tau at those epitopes and accelerated accumulation of somatodendritic tau. Moreover, OBX resulted in the elevation of calpain activity accompanied by an increased expression of the cyclin-dependent kinase 5 (cdk5) neuronal activators, p35 and p25, in hippocampus. Furthermore, OBX induces the loss of the cholinergic neurons in medial septal. Administration of cdk5 pharmacological inhibitor roscovitine into lateral ventricles suppressed tau hyperphosphorylation and mislocalization and restored the cholinergic neuron loss. These findings suggest that olfactory deprivation by OBX hastens tau pathology and cholinergic system impairment in htau mice possibly via activation of cdk5.